JP2018500312A - Disinfecting composition - Google Patents

Abstract

A disinfecting composition comprising a carboxy group-containing cellulose ester or a carboxy group-containing cellulose ether, a disinfectant, an alcohol, and water. Some embodiments further comprise a plasticizer. The compositions described herein can be used for disinfection of skin surfaces prepared for surgery.

Description

This application claims priority to US Provisional Patent Application No. 62 / 098,029, filed December 30, 2014, the disclosure of which is hereby incorporated by reference in its entirety. Incorporated into the book.

  The present invention relates to a disinfecting composition.

  Disinfecting the skin before performing invasive procedures such as surgery, anesthesia or catheterization has been a standard practice among clinicians for some time to reduce the risk of patient infection .

  Skin disinfection performed prior to invasive treatments such as surgery, catheterization or needle puncture with the goal of reducing the likelihood of infection is referred to as “prepping”. Compositions used as disinfectants during pretreatment are typically referred to as “prepping products”. An example known as a pre-treatment product is a disinfecting alcohol gel formulation containing a defined amount of alcohol, iodine and a thickener.

  Prior to performing an invasive procedure, surgical incise drapes are often used in addition to pre-treatment products. Surgical incision drapes are typically composed of a film substrate coated with an antimicrobial composition. The main function of the surgical drape is to prevent infection of the surgical site by preventing microbiota on the skin surface from entering the surgical site.

  As used herein, “Removal resistance” means that the disinfecting composition of the present invention maintains a film shape that adheres to the skin without peeling or dissolving under running water. means.

  “Drape Adhesive Strength” means that the disinfecting composition of the present invention has sufficient adhesive strength to adhere a surgical drape to the skin coated with such composition under conditions where there is an excess of moisture. To do.

  “Disinfection effect” means that the number of remaining bacterial colonies is small when the number of colonies is measured by the cup scrub method after the composition is applied to the skin.

  The present invention provides a disinfecting composition comprising a carboxy group-containing cellulose ester or a carboxy group-containing cellulose ether, a disinfectant, an alcohol, and water. In some embodiments, the composition further comprises a plasticizer.

  During surgery and other medical procedures, the area where the pretreatment product is applied is often the water or saline used by the clinician during a given procedure, or blood flowing out of the surgical site, etc. It is exposed to a large amount of moisture derived from it (hereinafter this situation is also referred to as “liquid loading environment”). Therefore, in order to exert efficacy, it is important that the pretreatment product maintain good adhesion to the patient's skin in a liquid loaded environment.

  The disinfecting composition of the present invention can be used as a pretreatment product, exhibits a high disinfecting effect, adheres very well to the skin, and in addition, the disinfectant contained in the composition is removed even in a liquid load environment (This characteristic is also referred to as “removal resistance” hereinafter). Furthermore, since the disinfecting composition described herein has film-forming ability, when applied to the skin, a film having excellent disinfecting properties and excellent removal resistance is formed. An adhesive film (which can be a surgical drape with a disinfectant or a surgical drape without a disinfectant) can be further laminated. Even when used in surgical drapes, the disinfecting compositions described herein exhibit excellent disinfecting effects, adhesion to the skin and resistance to removal.

  In a liquid-loaded environment, the adhesive strength to a surgical drape (hereinafter also referred to as “drape adhesive strength”) is typically reduced, which can eventually cause the surgical drape to detach from the skin. . Removal of the surgical drape from the skin creates a space where microorganisms can enter between the drape and the skin. By creating such a space, the infection prevention effect of the surgical drape is greatly lost.

  The disinfecting composition disclosed herein functions as a pre-operative skin disinfectant, exhibits removal resistance under liquid loading conditions, and can be used effectively in surgical incision drapes. it can. Furthermore, when the antiseptic composition further contains a plasticizer, such composition also exhibits improved drape adhesion strength.

  With respect to the disinfecting composition, a sustained film can be provided that forms a pre-operative skin disinfectant with a sufficient disinfecting effect, resistance to removal under liquid loading environments and excellent drape adhesive strength. That is, when applied to a surgical site, the disinfecting composition forms a highly durable film that has a disinfecting effect on the skin surface, and such disinfectant is exposed to water or saline used in surgery. It is difficult to be removed in an environment. In embodiments where the described disinfecting composition further comprises a plasticizer, removal of the surgical drape from the skin can also be inhibited.

  Further, with respect to the disinfecting composition disclosed herein, a continuous film having a disinfecting effect derived only from the disinfecting composition can be formed. Furthermore, in embodiments where the disinfecting composition further contains a plasticizer, the bond strength between the skin and the surgical drape is enhanced so that the composition exhibits a synergistic effect when used in combination with a surgical incision drape. It can also be made. Accordingly, a surgical drape used in combination with a disinfecting composition can be a surgical drape that does not have a disinfecting effect or a surgical drape that has a disinfecting effect (ie, a drape that includes an antimicrobial agent). When the disinfecting composition of the present invention is used in combination with a surgical drape having a disinfecting effect, the final disinfecting effect is improved.

Carboxy group-containing esters Examples of carboxy group-containing cellulose ester polymers suitable for use in the compositions disclosed herein include monoesters of cellulose derivatives such as hydroxyalkylalkyl cellulose and polycarboxylic acids. It is done. The carboxy group-containing cellulose ester is preferably a dicarboxylic acid monoester of hydroxyalkylalkyl cellulose. Examples of hydroxyalkylalkylcellulose dicarboxylic acid monoesters include hydroxyalkylalkylcellulose phthalates such as hydroxypropylmethylcellulose phthalate and hydroxyalkylalkylcellulose acetate succinates such as hydroxypropylcellulose acetate succinate. Further, the carboxy group-containing cellulose ester preferably further contains an aromatic ring in the chemical formula for the purpose of further improving the durability of the disinfectant. Examples of such carboxy group-containing cellulose esters include aromatic dicarboxylic acid monoesters of hydroxyalkylalkylcellulose, and among these, hydroxyalkylalkylcellulose phthalates such as hydroxypropylmethylcellulose phthalate (HPMCP) are particularly preferred. As the hydroxypropyl methylcellulose phthalate, HPMCP (available from Shin-Etsu Chemical Co., Ltd.) can be used, and as the hydroxypropyl cellulose acetate succinate, Shin-Etsu AQOAT (from Shin-Etsu Chemical Co., Ltd.) can be used. Available).

  In one embodiment, the upper limit of the carboxy group-containing cellulose ester polymer content is up to 10% based on the total weight of the disinfecting composition, in a further embodiment, the upper limit is up to 8%, and in a further embodiment The upper limit is up to 5%.

  In one embodiment, the lower limit of the carboxy group-containing cellulose ester content is at least 0.1% based on the total weight of the disinfecting composition, and in a further embodiment, the lower limit is at least 0.5%, and further In an embodiment, the lower limit is at least 1%.

Carboxy group-containing cellulose ether The carboxy group-containing cellulose ether is not particularly limited as long as it is a cellulose ether containing a carboxy group in the chemical formula. Examples of the carboxy group-containing cellulose ether include compounds obtained by esterifying a carboxylic acid having a halogen atom into a cellulose derivative such as hydroxyalkylalkylcellulose.

  Specific examples include carboxymethyl cellulose commercially available as Daicel CMC (available from Daicel FineChem Ltd.) and Cellogen (available from Dai-ichi Kogyo Seiyaku Co., Ltd.).

  In one embodiment, the upper limit of the carboxy group-containing cellulose ether content is up to 10% based on the total weight of the disinfecting composition, in another embodiment up to 8%, and in further embodiments up to 5%. %. In one embodiment, the lower limit of the content of carboxy group-containing cellulose ether is preferably at least 0.1% by mass of the total amount of the disinfecting composition, from the viewpoint that a disinfecting composition having excellent removal resistance can be provided. More preferably it is at least 0.5% by weight, even more preferably at least 1% by weight.

  In some embodiments of the disinfecting composition, a carboxy group-containing cellulose ester and a carboxy group-containing cellulose ether can be used in combination.

Disinfectant The disinfectant contained in the disinfecting composition may be any additive having a disinfecting effect. Examples of disinfectants include iodine, triiodide salts, povidone iodine, especially PEG derivatives such as povidone iodine USP, polyethylene glycol (PEG), PEG derivatives such as PEG surfactants, polymers and copolymers derived from N-vinyl pyrrolidone Formed iodophors such as iodine, sodium hypochlorite, phenol, cresol, triclosan, parachlorometaxylenol, isopropylmethylphenol and other phenolic disinfectants disclosed in US Patent Application Publication No. 2006/0052452; Quaternary ammonium disinfectant surfactants such as benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride and octenidine dihydrochloride, chlorhexidine salts such as chlorhexidine gluconate, alexidine, polyhedi Biguanides such as polymeric biguanides such as Samethylene Biguanide, other cationic disinfectants disclosed in US Patent Application Publication No. 2006/0051385, C8-C12 fatty acid esters of glycerin and propylene glycol, C7-C12 alkyl ethers of glycerin Antimicrobial lipids such as C6-C12 1,2 alkanediols and other antimicrobial lipids disclosed in US Patent Application Publication No. 2005/0089539, alkyldiaminoethylglycine hydrochloride, acrinol hydrate and hydrogen peroxide And natural oils and peroxides, as well as those disclosed in US Patent Application Publication No. 2006/0051384, and combinations thereof. The above-referenced patent applications are hereby incorporated by reference in their entirety.

  In one embodiment, the disinfectant is povidone iodine having a broad antimicrobial spectrum. Povidone iodine is desirable from the viewpoint that it is easy to confirm the presence or absence of a disinfectant because the applied site is colored. For disinfecting compositions that are colorless or do not have a color that is visible on most skin tones, suitable dyes can be used.

  In one embodiment, the disinfectant content is about 0.05% to about 20% by weight of the total amount of the disinfecting composition, and in a further embodiment about 0.25% to about 15% by weight. In another embodiment, from about 0.5% to about 10% by weight. Preferably, the disinfectant is present at greater than about 1%, more preferably at least greater than about 2%. In one embodiment, povidone iodine is used at about 5-10% by weight of the composition.

Alcohol The alcohol contained in the disinfecting composition is not particularly limited as long as it is a carboxy group-containing cellulose ester or a carboxy group-containing cellulose ether, and can disinfect the disinfectant sufficiently in water. Examples of alcohols include ethanol, propanol and isopropanol. Since the disinfecting composition of this embodiment is used by drying after application so as to form a film, an alcohol having a low boiling point and low skin irritation is preferable. In one embodiment, ethanol is used as the alcohol.

  In one embodiment, the alcohol content is about 10% to about 90% relative to the total weight of the disinfecting composition, and in a further embodiment, the alcohol content is about 20% to about 80%. In one embodiment, the alcohol content is greater than about 40% by weight, in a further embodiment greater than about 50% by weight, and in another embodiment greater than 60% by weight.

  In some embodiments, the alcohol content is about 1.5 to 4 times the weight of water.

Water Various water sources can be used in the composition of the present invention provided that the water is properly sterilized. In one embodiment, the water content is about 5% to about 50% by weight relative to the total weight of the disinfecting composition.

Plasticizer The antiseptic composition may further contain a plasticizer. The plasticizer reduces the glass transition temperature of the carboxy group-containing cellulose ester or carboxy group-containing cellulose ether as measured by differential scanning calorimetry of the polymer and plasticizer alone. Adding a plasticizer further provides plasticity, i.e., reduces the elasticity of the film. In some embodiments, a hydrophobic oil is used as the plasticizer. Examples of hydrophobic plasticizers include diisopropyl adipate, diisobutyl adipate, diisopropyl sebacate, isopropyl myristate and tri (capryl / caprylic acid) glycerin. In some embodiments, dicarboxylic acid esters such as C3-C8 alkyl alcohol esters of C4-C12 alkyl dicarboxylic acids such as diisopropyl adipate, diisobutyl adipate or diisopropyl sebacate were used as plasticizers.

  The plasticizer is a long chain linear or branched alkyl or alkenyl alcohol or short chain alkyl or aryl ester of an acid (C8 to C36) (C1 to C6) and their polyethoxylated derivatives; Short chain alkyl or aryl esters of C4 to C12 diacids or diols substituted with OH (C1 to C6); C4 to C18 alkyl or C6 to C24 aryl esters of polyhydroxy compounds such as glycerol, 2 to 10 glycerol units Sugar alcohols such as polyglycerin, xylitol and sorbitol, pentaerythritol, ethylene glycol, propylene glycol and their polyethoxylated derivatives and polyethylene glycol having C12-C22 alkyl group of polypropylene glycol Ter or ether; C1 to C8 alkyl esters of polyacids such as citric acid, trimellitic acid, phthalates, succinic acid, malic acid, tartaric acid and C4 to C12 diacids; C12 to C22 alkyl esters of polypropylene glycol / polyethylene glycol copolymers Or ether; long chain linear or branched alkyl or alkenyl alcohol or acid long chain (C8-C36) alkyl and alkenyl esters; long chain linear or branched (C8 to C36) alkyl or alkenyl amine or acid long chain It can be further selected from (C8-C36) alkyl and alkenylamides.

  In one embodiment, the plasticizer is present from about 1% to about 30% by weight relative to the weight of the bacterial composition. In a further embodiment, the plasticizer is present from about 5% to about 20%. As shown in the examples below, the addition of a plasticizer improves durability and drape bond strength.

  The disinfecting composition can be produced by mixing a carboxy group-containing cellulose ester or a carboxy group-containing cellulose ether, a disinfectant, alcohol and water. Furthermore, when the disinfectant is povidone iodine, it is preferable to add povidone iodine after mixing carboxy group-containing cellulose ester or carboxy group-containing cellulose ether, alcohol and water. When manufacturing the above-mentioned disinfecting composition, the temperature, mixing method, and the like can be appropriately changed by methods known to those skilled in the art.

  The present invention will be described in more detail below using examples and comparative examples, but the present invention is not limited to these examples.

  According to the content of Table 1, after mixing raw materials other than povidone iodine, povidone iodine was added to obtain compositions of Examples 1 to 3 and Comparative Examples 1 to 4. Unless indicated otherwise, the numerical values in Table 1 refer to “content (mass%)”.

Sustainability test 1
The sustainability of the disinfecting composition was evaluated by the following method. The compositions of Examples 1 and 2, the compositions of Comparative Examples 1 and 3, and ISODINE ™ (10% povidone iodine aqueous solution available from Meiji Seika Pharma Co., Ltd .; Reference Example 1) were euthanized, respectively. It was uniformly applied in an amount of 200 μL to the 2 cm × 2 cm area of the back skin of the pig. After the applied composition was completely dried, the application site was held at an angle of about 45 ° from the horizontal direction. Next, tap water was allowed to flow at a flow rate of about 2.5 L / min from a height of about 15 cm from the application site at 23-24 ° C. so that the water hits the composition directly and flows over the application area. The time until the brown color of the visible iodine disappeared was measured and recorded as the duration in Table 2.

  The compositions of Examples 1 and 2 containing a carboxy group-containing cellulose ester showed a superior duration than the compositions of Comparative Examples 1 and 3 containing a cellulose ester containing no carboxy group. In addition, the composition of Example 2 that further contained a plasticizer increased the retention time of the disinfectant by a factor of about 2 compared to the composition of Example 1 that did not contain the plasticizer. . The compositions of the examples and comparative examples showed a better disinfection duration than the composition of reference example 1.

Sustainability test 2
After mixing raw materials other than povidone iodine according to the contents in Table 3, povidone iodine was added to obtain the compositions of Examples 4 and 5 and the composition of Comparative Example 5. Unless indicated otherwise, the values in Table 3 refer to weight percent of the total composition.

  The duration of the disinfecting composition was evaluated by the following method. The compositions of Examples 4 and 5, the composition of Comparative Example 5 and the composition of Reference Example 1 were dropped in an amount of 200 μL onto the back skin of each euthanized pig, and 2 cm × 2 cm with a spatula. The area was spread evenly. After the applied composition was completely dried (after at least 5 minutes), the application site was tilted and held at about 45 ° from the horizontal direction. Next, tap water was allowed to flow at a flow rate of about 2.5 L / min from a height of about 15 cm from the application site at 23-24 ° C. so that the water hits the composition directly and flows over the application area. The time until the brown color of the visible iodine disappeared was measured and recorded as the duration in Table 4.

  The compositions of Examples 4 and 5 comprising a carboxy group-containing cellulose ester showed a superior duration than the composition of Comparative Example 5 comprising a cellulose ester containing no carboxy group. In particular, the composition of Example 4 showed better durability than the composition of Example 5.

Surgical drape adhesion test in a liquid-loaded environment 1
The composition of Example 2, the compositions of Comparative Examples 2 and 4, and the composition of Reference Example 1 were each uniformly applied to the area of about 4 cm × 12 cm of the back skin of the euthanized pig and allowed to stand for 20 minutes And dried completely. Antibacterial incision drape IOBAN ™ 2 (available from 3M) was cut into 0.5 inch (1.27 cm) wide strips, which were then adhered to the dried composition and uniformly The composition was crimped with a 4.5 pound (2.1 kg), 2 inch (5.1 cm) roller to achieve a good adhesion pressure. Each strip was allowed to sit for 30 minutes in order to provide an appropriate amount of adhesion. Next, gauze soaked in physiological saline was adhered to the top of the strip and allowed to stand for 20 minutes to create a liquid loading environment. Next, each strip was peeled using a Zwick Roell 7005 tensile strength measuring device at a peel angle of 90 ° and a speed of 12 inches / minute (30.5 cm / minute). The average value of the force (N) required to peel each sample over a length of at least 3 inches (7.6 cm) was recorded. At least four strips were evaluated for each composition. Table 5 shows the average values of the measured strengths.

  As shown in Table 5, the drape bond strength of Example 2 was superior to the drape bond strengths of Comparative Examples 2 and 4 and Reference Example 1.

Surgical drape adhesion test 2 in liquid loading environment
After mixing raw materials other than povidone iodine according to the contents of Table 6, povidone iodine was added to obtain compositions of Examples 6-9. As Reference Example 2, 3M DURAPREP Surgical Solution (trademark, available from 3M Company) was used. Unless indicated otherwise, the values in Table 6 refer to weight percent.

  A drape adhesion test was performed on the compositions of Examples 6-9 and Reference Examples 1 and 2 as described below. Each composition was impregnated into foam and applied to pig skin that had been cut and divided in advance. After application, the composition was left to dry for 20 minutes. Antibacterial incision drape IOBAN ™ 2 (available from 3M) was cut into 0.5 inch (1.27 cm) wide strips, which were then adhered to the dried composition and uniformly The composition was crimped with a 4.5 pound (2.1 kg), 2 inch (5.1 cm) roller to achieve a good adhesion pressure. Each strip was allowed to sit for 30 minutes in order to provide an appropriate amount of adhesion. Next, gauze soaked in physiological saline was adhered to the top of the strip and allowed to stand for 20 minutes to create a liquid loading environment. Next, each strip was peeled using a Zwick Roell 7005 tensile strength measuring device at a peel angle of 90 ° and a speed of 12 inches / minute (30.5 cm / minute). The average value of the force (N) required to peel each sample over a length of at least 3 inches (7.6 cm) was recorded. At least four strips were evaluated for each composition. Table 7 shows the average values of the measured strengths.

  As shown in Table 5, the drape bond strength of Example 2 was superior to the drape bond strengths of Comparative Examples 2 and 4 and Reference Example 1.

Disinfection effect test The disinfection effect was confirmed using the composition of Example 3, the composition of Reference Example 1, and 3M One-step Patient Prep (7.5% povidone iodine aqueous solution, available from 3M Company; Reference Example 3). did. The skin of the abdomen of the euthanized pig was divided into a grid of about 2.5 inches × 2.5 inches, and each composition was applied. As the application site of each composition, at least three sections were randomly selected for each composition, and the application sites were uniformly and continuously assigned to the upper and lower parts of the abdominal skin. The coating method used for the disinfecting composition of Reference Example 1 was a conventional coating method in a Japanese processing room environment where gauze immersed in a large amount of solution was applied. That is, the composition was applied with gauze so as to draw a circle from the center to the outside of the skin section. This was repeated three times. Furthermore, in the method for applying the composition of Reference Example 3, the composition was applied to the skin of pigs using a unique one-step applicator system. The composition of Example 3 was applied to the skin surface using a one-step applicator system having a container for containing the solution and a foam sponge secured to the top of the container filled with the solution. This served as a holder for the disinfecting composition during the pretreatment. That is, based on the design specifications of the applicator and the user manual, both compositions were obtained by rubbing the composition of Reference Example 3 and Example 3 against the skin for 30 seconds using a foam sponge so that the same arrangement overlapped. The object was applied.

  After applying each composition to the application site using gauze or foam sponge, the composition was allowed to stand for 10 minutes until it completely dried. Next, using the “cup scrub method” (ASTM E1874), surviving bacteria were recovered and the number of colonies of surviving bacteria was measured. That is, a sterile scrub cup was placed on the skin to which the composition was applied, 2.5 mL of the sampling solution was added, and the site was rubbed with a rubber policeman (plastic scrub stick) for 1 minute. After 1 minute, the sampling solution was transferred to a 15 mL tube. Each step was repeated in the same manner so that the amount of the sampling solution was finally 5 mL. By the same method, the number of viable bacteria of the negative control (baseline) was sampled and measured in three untreated skin portions. After serial dilution of each sample (10-fold, 100-fold and 1000-fold), this sample was cultured on a plate. Next, the cultured sample was incubated at 37 ° C. for 3 days, and the number of colonies was measured. Table 8 shows common logarithmic values (Log CFU / mL) of the obtained number of surviving bacteria.

  The composition of Example 3 showed a better disinfection effect than Reference Examples 1 and 3.

Suitability test According to the contents shown in Table 9 or Table 10, hydroxypropylmethylcellulose phthalate, plasticizer (diisopropyl adipate, tri (capryl / caprylic acid) glycerin or isopropyl myristate), povidone iodine and ethanol were mixed. Next, the appearance of the composition when water was added and stirred was observed.

  The results are shown in Table 11. In Example 10 containing diisopropyl adipate, a colorless and transparent composition was obtained. The raw material did not dissolve and the composition became cloudy.

  The contents of all patents, patent applications and publications and electronically available articles cited herein are incorporated by reference. In case of a conflict between the present disclosure and the disclosure of a document incorporated herein by reference, the present disclosure shall prevail. The foregoing detailed description and examples have been given for clarity of understanding only. This does not make unnecessary limitations. The invention is not limited to the exact details shown and described, but variations obvious to one skilled in the art are included within the scope of the invention as defined by the claims.

  All headings are for the convenience of the reader and are not used to limit the meaning of the text following the heading, unless otherwise specified.

  The present invention described as an example in the present specification can be suitably executed without any elements not specifically disclosed in the present specification. Thus, for example, in any case herein, any of the terms “comprising”, “consisting essentially of” and “consisting of” It can be replaced with either of the other two terms. The terms and phrases used are intended to be illustrative rather than limiting, and the use of such terms and phrases is not intended to exclude the equivalents of the features shown and described or portions thereof, It will be understood that various modifications are possible within the scope of the claimed invention. Thus, although the present invention has been specifically disclosed by means of preferred embodiments and optional features, modifications and variations of the concepts disclosed herein can be used by those skilled in the art. It should be understood that modifications and variations are considered to be within the scope of the invention as defined by the appended claims.

Claims (11)

  A disinfecting composition comprising a carboxy group-containing cellulose ester or a carboxy group-containing cellulose ether, a disinfectant, an alcohol, and water.   The composition for bacteria of Claim 1 in which the said composition contains the carboxy-group containing cellulose ester which is the dicarboxylic acid monoester of hydroxyalkyl alkyl cellulose.   The disinfecting composition according to claim 2, wherein the composition comprises a carboxy group-containing cellulose ester selected from the group consisting of hydroxypropylmethylcellulose phthalate and hydroxypropylcellulose acetate succinate.   The disinfecting composition according to claim 3, wherein the carboxy group-containing cellulose ester is hydroxypropylmethylcellulose phthalate.   The bacterial composition according to claim 1, wherein the composition comprises a carboxy group-containing ether that is a hydroxyalkylalkylcellulose.   The composition for bacteria of Claim 5 whose carboxy group containing ether is carboxymethylcellulose.   The disinfecting composition according to any one of claims 1 to 3, further comprising a dicarboxylic acid ester.   The composition for bacteria according to claim 1, wherein the disinfectant is selected from the group consisting of iodine, triiodide salt and iodophor.   9. A disinfecting composition according to claim 8, wherein the disinfectant is an iodophor.   The disinfectant povidone iodine composition according to claim 9, wherein the disinfectant is povidone iodine.   The bacterial composition according to claim 1, wherein the ester or ether further comprises an aromatic ring.